My daughter had Beriberi
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I practiced primary care for five years and worked 50-hour weeks, seeing 40 patients daily. I saw many patients without insurance, exposing me to complex and unusual cases. I also spent a two-year primary care rotation as a PA student at that same clinic (our program had us in the clinic in the second quarter of school). After seven years, I saw and learned more than I ever thought I could.
Then, in 2021, I was introduced to a teacher who would push me past every physical, spiritual, emotional, and intellectual limit I thought existed. Chloe (my daughter) was born with a primary mitochondrial disease (86% heteroplasmy) and various autoimmune abnormalities, both of which can affect any organ system and present with any symptom imaginable.
My daughter has visited more hospitals, been examined by more doctors, and has had more blood drawn than my wife and I put together. But, if you were to meet her, you would never know. During our last rheumatology appointment, her doctor was amazed and dumbfounded by the turn of events. She'd never seen a patient so young worsen and improve the way Chloe did. Although she may not know what happened, I can tell you this was not an accident. Every part of her health journey has been very intentional.
The moment she was diagnosed, the clock started ticking.
There aren't words to express my fear, sadness, and anger. My urgency to learn spawned out of fear that I would lose her. According to the literature, kids with this mutation and heteroplasmy level will experience neurological complications during a febrile illness. This is the perfect storm where the energy demands far exceed the available ATP necessary to keep things working correctly. The energy requirements increase further when you add a dysfunctional immune system (autoimmunity).
It feels like I'm in a residency, working and studying 80 hours a week, expecting to apply everything I'm learning immediately. But, trying to figure out what a one-year-old is feeling/experiencing is no easy feat; they don't have the language to express their complex symptoms. I have learned to appreciate the history and physical exam more than ever. Unfortunately, this is often replaced by a test in clinical practice and has become a lost art.
It started with Roseola
About five weeks ago, Chloe started having a 102-degree fever that we couldn't keep down with Tylenol. Because of her thrombocytopenia and mitochondrial disease, we avoid ibuprofen. Also, if it weren't for the mitochondrial mutation and needing to conserve as much ATP as possible, I wouldn't fret so much about reducing her fever.
After three days, she developed a rash over her chest and back that quickly spread to her extremities and face. Classically, the fever tends to resolve in Roseola as soon as the rash starts, but in our case, it continued for five days. She also had sleep disruptions, resulting in only five hours of sleep at night without being able to nap. This entire time, she only ate 300-400 calories daily.
This went on for two weeks, at which point she had lost 1.5 pounds; this was a lot, seeing as she was already in the 1% for her age. Then, I began to notice staring spells, a loss of coordination, and what seemed to be paresthesias. She wasn't able to describe the neuropathy, but I noticed she would stare at her hands and feet frequently with a confused look; on separate occasions, she said her hand, foot, and calf hurt. Lastly, she had episodes of being very irritable and uncomfortable, followed by normalcy.
This was the perfect storm for an acute decompensation to occur. Energy demands were sky-high, yet she had no desire to eat. I have never been more worried in my life.
But the universe tends to provide the answers, so long as you're looking. Luckily, I happened to be working on a case study for my master's in nutrition regarding thiamine deficiency. Then, I had a lightbulb moment.
Chloe had Beriberi!
I immediately started her on 100mg of thiamine. Due to various absorption rates, I gave her a combination of 25 mg of thiamine hydrochloride, 25 mg of thiamine monophosphate, and 50 mg of benfotiamine. Within 24 hours, we saw a dramatic improvement in sleep, appetite, and mood. After a couple of days, I noticed an improvement in neurological symptoms.
It was an incredible transformation to witness!
Beriberi is a clinical manifestation of thiamine deficiency and can be further divided into dry Beriberi (nervous system involvement), wet Beriberi (cardiovascular involvement), and infantile Beriberi. Thiamine deficiency can also present with Wernicke-Korsakoff syndrome, characterized by acute encephalopathy (Wernicke encephalopathy), followed by chronic amnestic syndrome (Korsakoff syndrome).
A deficiency can result from poor nutritional intake, decreased absorption, increased thiamine loss, or increased requirements. We were in a situation that increased requirements and decreased dietary intake. Because thiamine is poorly stored in the body, a deficiency can occur quickly (days to weeks).
Magnesium (decreased intake), ATP (decreased production from a decrease in thiamine with a mitochondrial mutation), and thiamine pyrophosphokinase convert thiamine to thiamine pyrophosphate (the active form) in the cytoplasm of the cell.
Thiamine pyrophosphate is then transported into the mitochondria, where it is a cofactor for the enzymes (transketolase, alpha-ketoglutarate dehydrogenase, and pyruvate dehydrogenase) involved in glucose and amino acid metabolism and the synthesis of neurotransmitters. The impairment of ATP and neurotransmitter production results in neurological impairment.
Interestingly enough, the anorexia and early satiety were protecting our daughter. An increase in food (carbs and protein) would require an increase in thiamine, leading to further deterioration.
When I stop to appreciate human physiology, I can’t help but marvel at the intricacies responsible for keeping us in homeostasis.
It's been five weeks since the infection, and we've officially returned to baseline. This was a very long and challenging month, but it was well worth the effort to see our baby girl thriving again. Before bed last night, she showed off her first jump (both feet left the ground) as she tried to get the remote to change the channel, lol. This milestone has added significance because early on, Chloe had muscular weakness from mitochondrial myopathy (which is now almost non-existent).